The use of urinary biomarkers in the diagnosis of overactive bladder in female patients. A systematic review and meta-analysis

Introduction and hypothesis Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and other proteins are related to overactive bladder (OAB) syndrome, as their urinary concentrations are significantly different from those of the general non-OAB population. This review aims to systematically assess whether NGF, BDNF, and other urinary by-products can be used as potential biomarkers to manage women with OAB. Methods This was a systematic review and metanalysis that was conducted according to PRISMA guidelines. Studies were identified by electronic search of Medline, Scopus, ScienceDirect, Embase, and Cochrane Register until October 2020. The included studies investigated the correlation of OAB with NGF, BDNF, and other potential biomarkers in symptomatic women and their controls. Results Twelve studies (581 female OAB patients and 394 female controls) were included. Urinary NGF, NGF/Cr, BDNF/Cr, ATP/Cr, and PGE2/Cr ratios were identified as potential biomarkers in female OAB patients. Results of the meta-analysis indicated that uNGF [standard mean difference (SMD) 1.45, 95% CI 0.53-2.36], NGF/Cr ratio (SMD 1.23, 95% CI 0.67-1.78), BDNF/Cr ratio (SMD 0.78, 95% CI 0.006-1.50), and BDNF/Cr ratio (RR 0.78, 95% CI 0.006-1.50) were increased in female OAB patients compared to healthy controls, whereas no difference was found for the PGE2/Cr and ATP/Cr ratios. Current data are inadequate to assess any other potential biomarkers, such as urinary MDA, ATP, and cytokines, in the management of OAB in female patients. Conclusions uNGF, NGF/Cr, and BDNF/Cr ratio could be used in the assessment of female OAB patients. Further studies are needed to specify OAB urinary titer levels in OAB subgroups and healthy women and their potential as diagnostic and management tools in OAB women.